Carcinogenesis, Teratogenesis & Mutagenesis

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The association of cervical lesion pathogenesis in Uighur women and promoter methylation of CALCA gene

Tuerxunpaxia·WUBULIKASIMU1,Abida·ABUDOUKADEER2,SHENG Lei3,Abulizi·ABUDULA 1,3,*   

  1. 1. Department of Biochemistry, College of Basic Medicine, Xinjiang Medical University, Urumqi 830011; 2. Gynecological Department of the First Affiliated Hospital, Xinjiang Medical University,Urumqi 830011; 3. Xinjiang Key Laboratory of Molecular Biology and Endemic Diseases, Xinjiang Medical University, Urumqi 830011, Xinjiang, China
  • Received:2012-07-26 Revised:2012-12-24 Online:2013-03-30 Published:2013-03-30
  • Contact: Abulizi?ABUDULA,E-mail:abulizi_a@126.com

Abstract:

OBJECTIVE: To study the association of cervical lesion development of Uighur women with CpG site specific methylation of calcitonin-related polypeptide alpha (CALCA) gene at the promoter region,to further reveal the epigenetic regulatory mechanisms of this gene expression in cervical cancer. METHODS:We collected 50 samples of fresh tissues in Uighur women with cervicitis(16 cases),cervical intraepithelial neoplasia (CIN) (9 cases) and cervical squamous cell carcinoma(CSCC)(25 cases). We analyzed quantitatively the CpG methylation level of CALCA at the promoter region in tissue DNA by Sequenom MassARRAY platform. RESULTS:We found target CpG fragment methylation of CALCA at the promoter region specific to papillary thyroid cancer with statistical difference,in comparison to the normal control. Further analysis of CALCA for single CpG site methylation indicated that the methylation of CpG-2,CpG-3,CpG-9.10.11 and CpG-12 was quantitatively higher in cancer tissue DNA than in the normal,and also correlated with the degree of clinical stages(P<0.05) . Although cervical lesion development was associated with the alteration of methylation ratio of target CpG fragment at the promoter region of CALCA,i.e. low in cervicitis (0.22),increased in CIN (0.26),and highest in CSCC (0.36),significant difference was only found between CSCC and cervicitis (P<0.05). Methylation ratios of six CpG sites including CpG-2,CpG-3,CpG-9/CpG-10/CpG-11 and CpG-12 were significantly higher in CSCC than in CIN or cervicitis (P<0.05). CONCLUSION:The methylation of CALCA gene promoter was closely associated with the development of cervical cancer in Uighur women,and the alteration in the methylation level of certain CpG sites may become a molecular marker for early diagnosis of cervical carcinogenesis.

Key words: CALCA, promoter, methylation, cervical carcinoma of Uighur women, CpG site